Central signalling cross-talk between insulin and leptin in glucose and energy homeostasis.
Boucsein A; Centre for Neuroendocrinology, Department of Physiology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand.
Kamstra K; Centre for Neuroendocrinology, Department of Physiology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand.
Tups A; Centre for Neuroendocrinology, Department of Physiology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand.; Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland, New Zealand.
Journal of neuroendocrinology [J Neuroendocrinol] 2021 Apr; Vol. 33 (4), pp. e12944. Date of Electronic Publication: 2021 Feb 21.
Typ publikacji :
Journal Article; Review
Imprint Name(s) :
Publication: <2010->: Malden, MA : Wiley & Sons
Original Publication: Eynsham, Oxon, UK : Oxford University Press, c1989-
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Grant Information :
Maurice Wilkins Centre for Molecular Biodiscovery
Contributed Indexing :
Keywords: circadian clock; energy metabolism; evolution; hypothalamus; wnt signalling
Entry Date(s) :
Date Created: 20210222 Latest Revision: 20210419
Update Code :
Energy homeostasis is controlled by an intricate regulatory system centred in the brain. The peripheral adiposity signals insulin and leptin play a crucial role in this system by informing the brain of the energy status of the body and mediating their catabolic effects through signal transduction in hypothalamic areas that control food intake, energy expenditure and glucose metabolism. Disruptions of insulin and leptin signalling can result in diabetes and obesity. The central signalling cross-talk between insulin and leptin is essential for maintenance of normal healthy energy homeostasis. An important role of leptin in glucoregulation has been revealed. Typically regarded as being controlled by insulin, the control of glucose homeostasis critically depends on functional leptin action. Leptin, on the other hand, is able to lower glucose levels in the absence of insulin, although insulin is necessary for long-term stabilisation of euglycaemia. Evidence from rodent models and human patients suggests that leptin improves insulin sensitivity in type 1 diabetes. The signalling cross-talk between insulin and leptin is likely conveyed by the WNT/β-catenin pathway. Leptin activates WNT/β-catenin signalling, leading to inhibition of glycogen synthase kinase-3β, a key inhibitor of insulin action, thereby facilitating improved insulin signal transduction and sensitisation of insulin action. Interestingly, insights into the roles of insulin and leptin in insects and fish indicate that leptin may have initially evolved as a glucoregulatory hormone and that its anorexigenic and body weight regulatory function was acquired throughout evolution. Furthermore, the regulation of both central and peripheral control of energy homeostasis is tightly controlled by the circadian clock, allowing adaptation of homeostatic processes to environmental cues.
(© 2021 British Society for Neuroendocrinology.)